Pub Date : 2026-02-20Epub Date: 2026-01-15DOI: 10.1016/j.ijpharm.2026.126596
Mingrui Ma , Marwa Nassar , Jason Teckoe , J. Axel Zeitler
Titanium dioxide (TiO2) is often used as a white base pigment in film coatings, but recent EU restrictions on its use in food have prompted pharmaceutical manufacturers to seek alternatives. Terahertz pulsed imaging (TPI) was used to examine the hydration of TiO2-free immediate release formulations, either without an opacifier or using calcium carbonate (CaCO3). The coatings, made from polyvinyl alcohol (PVA) or hydroxypropyl methylcellulose (HPMC), were approximately 100 µm thick. TPI results indicated that the type of film coating influenced hydration and scattering effects. However, there was no evidence that TiO2-free coatings compromised tablet disintegration. Although the HPMC coating with CaCO3 gelled upon hydration, the tablets fully hydrated within the required time. These findings offer insights into the mechanistic impacts of alternative coatings in the industry.
{"title":"Terahertz imaging of titanium dioxide-free film coating hydration and tablet core interactions","authors":"Mingrui Ma , Marwa Nassar , Jason Teckoe , J. Axel Zeitler","doi":"10.1016/j.ijpharm.2026.126596","DOIUrl":"10.1016/j.ijpharm.2026.126596","url":null,"abstract":"<div><div>Titanium dioxide (TiO<sub>2</sub>) is often used as a white base pigment in film coatings, but recent EU restrictions on its use in food have prompted pharmaceutical manufacturers to seek alternatives. Terahertz pulsed imaging (TPI) was used to examine the hydration of TiO<sub>2</sub>-free immediate release formulations, either without an opacifier or using calcium carbonate (CaCO<sub>3</sub>). The coatings, made from polyvinyl alcohol (PVA) or hydroxypropyl methylcellulose (HPMC), were approximately 100<!--> <!-->µm thick. TPI results indicated that the type of film coating influenced hydration and scattering effects. However, there was no evidence that TiO<sub>2</sub>-free coatings compromised tablet disintegration. Although the HPMC coating with CaCO<sub>3</sub> gelled upon hydration, the tablets fully hydrated within the required time. These findings offer insights into the mechanistic impacts of alternative coatings in the industry.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"691 ","pages":"Article 126596"},"PeriodicalIF":5.2,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10Epub Date: 2025-12-21DOI: 10.1016/j.ijpharm.2025.126522
Noemí Dorival-García , Gareth Lomasney , Jonathan Bones
Cell therapies (CT) have demonstrated life-changing benefits and curative options to patients with unmet medical needs. Recent commercial successes have strengthened support for the industry; strong clinical responses are propelling additional CT products toward commercialisation. However, manufacturing of CT products continues to create challenges. Extractables and leachables (E&Ls) are a significant concern for the CT industry, which relies exclusively on single-use systems (SUSs). Investigation of the impact of SUS materials that encounter the cell-based product is a new field and the generation of more information is critical. Here, a proof-of-principle study is presented, demonstrating evidence of effects of leachates on T cells. Jurkat cells, a prototypical T cell line, were cultivated in media previously incubated in single-used bags (SUBs) utilised during incubation/expansion stages. Leachables present in the media were identified by high resolution mass spectrometry (HRAM). The physiological condition of T-cells was assessed using biological assays. Media components and metabolites were analysed over time using a direct infusion-mass spectrometry (DI-MS) method. Media containing leachables resulted in cell growth inhibition and early onset of the apoptosis/necrosis pathways. Changes in mitochondrial membrane potential suggested that leachables are cytotoxic via ΔΨm depolarisation, involving the intrinsic apoptotic pathway in the initiation of cell death. Key metabolic pathways were also significantly affected, producing accumulation of toxic metabolites and degradation of nucleic acids and lipids.
{"title":"Assessing effects of leachables in single-use systems used in cell therapy manufacture","authors":"Noemí Dorival-García , Gareth Lomasney , Jonathan Bones","doi":"10.1016/j.ijpharm.2025.126522","DOIUrl":"10.1016/j.ijpharm.2025.126522","url":null,"abstract":"<div><div>Cell therapies (CT) have demonstrated life-changing benefits and curative options to patients with unmet medical needs. Recent commercial successes have strengthened support for the industry; strong clinical responses are propelling additional CT products toward commercialisation. However, manufacturing of CT products continues to create challenges. Extractables and leachables (E&Ls) are a significant concern for the CT industry, which relies exclusively on single-use systems (SUSs). Investigation of the impact of SUS materials that encounter the cell-based product is a new field and the generation of more information is critical. Here, a proof-of-principle study is presented, demonstrating evidence of effects of leachates on T cells. Jurkat cells, a prototypical T cell line, were cultivated in media previously incubated in single-used bags (SUBs) utilised during incubation/expansion stages. Leachables present in the media were identified by high resolution mass spectrometry (HRAM). The physiological condition of T-cells was assessed using biological assays. Media components and metabolites were analysed over time using a direct infusion-mass spectrometry (DI-MS) method. Media containing leachables resulted in cell growth inhibition and early onset of the apoptosis/necrosis pathways. Changes in mitochondrial membrane potential suggested that leachables are cytotoxic via ΔΨm depolarisation, involving the intrinsic apoptotic pathway in the initiation of cell death. Key metabolic pathways were also significantly affected, producing accumulation of toxic metabolites and degradation of nucleic acids and lipids.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126522"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145819294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10Epub Date: 2026-01-07DOI: 10.1016/j.ijpharm.2026.126581
Simone Misto , Teresa Ferrillo , Sandor Balog , Fabiana Quaglia , Thomas Lee Moore
Lipid nanoparticle-borne, RNA-based therapeutics have emerged as transformative tools in nanomedicine. However, to optimize lipid nanoparticle (LNP) formulations against different pathologies, it will be necessary to change LNP payload, lipid composition, and production parameters. High-throughput formulation screening provides a way to rapidly develop and assess new LNP formulations, however this requires the capacity for high-throughput LNP physico-chemical characterization methods. When considering a shift towards automated/semi-automated high-throughput methods, it is pertinent to evaluate whether such characterization is comparable to so-called “tried and true” methods, especially in the context of scaling hit formulations from the screening phase to production. Here, we show that combining a semi-automated microfluidic system with a high-throughput characterization instrument enables the rapid production and characterization of LNP. Compared to conventional methods, the high-throughput plate reader DLS provided comparable hydrodynamic diameter data and faster analysis, albeit with lower sensitivity for RNA quantification. Additionally, we conducted an independent analysis of raw autocorrelation function data from dynamic light scattering measurements to mitigate functional differences between the high-throughput and single sample instruments. Fluorescence-based assays, also capable for high-throughput workflows, were demonstrated to be more sensitive for RNA quantification. These results illustrate that high-throughput systems can streamline LNP development, and be integrated into a translational workflow, i.e. screening to identify hit formulations, transition of hit formulations to scalable production methods, and validation of screening characterization results. This integrated workflow represents an important step for RNA therapeutic development pipelines, where increasing characterization capacity can accelerate nanomedicine development.
{"title":"Comparison and validation of a high-throughput lipid nanoparticle production and characterization workflow","authors":"Simone Misto , Teresa Ferrillo , Sandor Balog , Fabiana Quaglia , Thomas Lee Moore","doi":"10.1016/j.ijpharm.2026.126581","DOIUrl":"10.1016/j.ijpharm.2026.126581","url":null,"abstract":"<div><div>Lipid nanoparticle-borne, RNA-based therapeutics have emerged as transformative tools in nanomedicine. However, to optimize lipid nanoparticle (LNP) formulations against different pathologies, it will be necessary to change LNP payload, lipid composition, and production parameters. High-throughput formulation screening provides a way to rapidly develop and assess new LNP formulations, however this requires the capacity for high-throughput LNP physico-chemical characterization methods. When considering a shift towards automated/semi-automated high-throughput methods, it is pertinent to evaluate whether such characterization is comparable to so-called “tried and true” methods, especially in the context of scaling hit formulations from the screening phase to production. Here, we show that combining a semi-automated microfluidic system with a high-throughput characterization instrument enables the rapid production and characterization of LNP. Compared to conventional methods, the high-throughput plate reader DLS provided comparable hydrodynamic diameter data and faster analysis, albeit with lower sensitivity for RNA quantification. Additionally, we conducted an independent analysis of raw autocorrelation function data from dynamic light scattering measurements to mitigate functional differences between the high-throughput and single sample instruments. Fluorescence-based assays, also capable for high-throughput workflows, were demonstrated to be more sensitive for RNA quantification. These results illustrate that high-throughput systems can streamline LNP development, and be integrated into a translational workflow, i.e. screening to identify hit formulations, transition of hit formulations to scalable production methods, and validation of screening characterization results. This integrated workflow represents an important step for RNA therapeutic development pipelines, where increasing characterization capacity can accelerate nanomedicine development.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126581"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145944154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10Epub Date: 2025-12-31DOI: 10.1016/j.ijpharm.2025.126552
Kaixin Feng , Zhongkun Zhang , Jingjing Zhang , Xiaohan Xia , Siyu Yao , Yufei Wang , Min Wu
Doxorubicin (DOX) is limited by its clinical toxicity as a breast cancer therapy. Traditional liposomal formulations improve the tumor delivery of DOX but suffer from inadequate controlled release and low encapsulation efficiency of DOX. To address these, we developed a photo-responsive liposomal formulation DTTPL by co-encapsulating DOX and TiO2 nanostructures (TiO2) within D-α-tocopheryl succinate (α-TOS)-PEG liposomes. DTTPL successfully facilitated the release of DOX through the light-sensitive catalysis mechanism of TiO2, exhibiting 4.6 times greater cytotoxicity against MCF-7 cells compared to free DOX. Transcriptional analysis revealed synergistic DOX/DTTPL dysregulation of key genes (Brca1, Bcl-2, Bax, Caspase-3), aligning with cytotoxicity. Eventually, light-triggered DOX/DTTPL formulation resulted in 70.09% of tumor growth inhibition (TGI) in mice with no significant organ toxicity. This photo-responsive nanoformulation enables efficient controlled release of DOX, offering an alternative strategy for small molecule delivery to treat triple negative breast cancer.
{"title":"Light-responsive α-TOS liposomal nanocarriers Co-delivering TiO2 and doxorubicin for the treatment of breast cancer","authors":"Kaixin Feng , Zhongkun Zhang , Jingjing Zhang , Xiaohan Xia , Siyu Yao , Yufei Wang , Min Wu","doi":"10.1016/j.ijpharm.2025.126552","DOIUrl":"10.1016/j.ijpharm.2025.126552","url":null,"abstract":"<div><div>Doxorubicin (DOX) is limited by its clinical toxicity as a breast cancer therapy. Traditional liposomal formulations improve the tumor delivery of DOX but suffer from inadequate controlled release and low encapsulation efficiency of DOX. To address these, we developed a photo-responsive liposomal formulation DTTPL by co-encapsulating DOX and TiO<sub>2</sub> nanostructures (TiO<sub>2</sub>) within D-α-tocopheryl succinate (α-TOS)-PEG liposomes. DTTPL successfully facilitated the release of DOX through the light-sensitive catalysis mechanism of TiO<sub>2</sub>, exhibiting 4.6 times greater cytotoxicity against MCF-7 cells compared to free DOX. Transcriptional analysis revealed synergistic DOX/DTTPL dysregulation of key genes (Brca1, Bcl-2, Bax, Caspase-3), aligning with cytotoxicity.<!--> <!-->Eventually, light-triggered DOX/DTTPL formulation resulted in 70.09% of tumor growth inhibition (TGI) in mice with no significant organ toxicity. This photo-responsive nanoformulation enables efficient controlled release of DOX, offering an alternative strategy for small molecule delivery to treat triple negative breast cancer.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126552"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10Epub Date: 2025-12-28DOI: 10.1016/j.ijpharm.2025.126529
Shelly Keisar , Qonita Kurnia Anjani , Abraham M. Abraham , Lalitkumar K. Vora , Eneko Larrañeta , Ryan F. Donnelly , Aiman Abu Ammar
Microneedles (MNs) are micro-sized needles that were originally designed as minimally invasive and painless devices capable of piercing the main skin barrier, the stratum corneum, without stimulating nerve fibers, showing promising prospects as an alternative to other drug administration routes. Poly (lactic-co-glycolic acid) (PLGA) is a biodegradable and biocompatible copolymer with favorable mechanical properties, making it particularly suitable for fabrication of MNs for controlled-release drug delivery. This review provides a comprehensive overview of the design, fabrication, and therapeutic potential of PLGA-based MN systems across a broad range of applications, including transdermal systemic delivery, vaccine delivery and topical skin applications. Due to their exceptional virtues, PLGA MNs are further utilized in nontransdermal applications such as ocular, oral cavity, nasal, and other emerging uses that are presented. Eventually, toxicity and safety profile are discussed, and a concluding section on future perspectives is provided.
{"title":"Poly (lactic-co-glycolic acid)-based microneedles for drug delivery across different biological barriers","authors":"Shelly Keisar , Qonita Kurnia Anjani , Abraham M. Abraham , Lalitkumar K. Vora , Eneko Larrañeta , Ryan F. Donnelly , Aiman Abu Ammar","doi":"10.1016/j.ijpharm.2025.126529","DOIUrl":"10.1016/j.ijpharm.2025.126529","url":null,"abstract":"<div><div>Microneedles (MNs) are micro-sized needles that were originally designed as minimally invasive and painless devices capable of piercing the main skin barrier, the <em>stratum corneum</em>, without stimulating nerve fibers, showing promising prospects as an alternative to other drug administration routes. Poly (lactic-co-glycolic acid) (PLGA) is a biodegradable and biocompatible copolymer with favorable mechanical properties, making it particularly suitable for fabrication of MNs for controlled-release drug delivery. This review provides a comprehensive overview of the design, fabrication, and therapeutic potential of PLGA-based MN systems across a broad range of applications, including transdermal systemic delivery, vaccine delivery and topical skin applications. Due to their exceptional virtues, PLGA MNs are further utilized in nontransdermal applications such as ocular, oral cavity, nasal, and other emerging uses that are presented. Eventually, toxicity and safety profile are discussed, and a concluding section on future perspectives is provided.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126529"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145862473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10Epub Date: 2025-12-26DOI: 10.1016/j.ijpharm.2025.126524
Siqi Wang, Rand Z. Murtadha, R. Karl Malcolm
There have been several significant advances in recent years around long-acting strategies for HIV pre-exposure prophylaxis, including DapiRing® (a 1-month dapivirine (DPV)-releasing vaginal ring), Apretude® (a cabotegravir intramuscular injection administered every two months), and Yeztugo® (a twice-yearly lenacapavir injection). With the goal of developing new drug delivery devices that can extend antiretroviral release for 12 months or longer, we report here our preliminary efforts to design a subdermal implant releasing the antiretroviral drug DPV. These reservoir-type rod implants (length 40 mm, cross-sectional diameters 2.5, 3.2, 3.5 or 4.0 mm) comprised a silicone elastomer core containing solid crystalline DPV (loading 10, 20 or 40 % w/w) and an open-ended non-medicated rate-controlling silicone elastomer membrane (thickness 0.5, 0.8 or 1.0 mm). DPV in vitro release rates could be modulated by adjusting the membrane thickness. Continuous in vitro DPV release ∼12 μg/day was demonstrated over 330 days, with sufficient residual drug content (∼87 mg/∼95 %) to extend release for at least 5 years. In particular, the study highlights the challenges in designing subdermal implants providing sufficient DPV release to maintain systemic/vaginal concentrations at protective levels.
{"title":"Formulation development of a dapivirine-releasing subdermal implant for HIV prevention","authors":"Siqi Wang, Rand Z. Murtadha, R. Karl Malcolm","doi":"10.1016/j.ijpharm.2025.126524","DOIUrl":"10.1016/j.ijpharm.2025.126524","url":null,"abstract":"<div><div>There have been several significant advances in recent years around long-acting strategies for HIV pre-exposure prophylaxis, including DapiRing® (a 1-month dapivirine (DPV)-releasing vaginal ring), Apretude® (a cabotegravir intramuscular injection administered every two months), and Yeztugo® (a twice-yearly lenacapavir injection). With the goal of developing new drug delivery devices that can extend antiretroviral release for 12 months or longer, we report here our preliminary efforts to design a subdermal implant releasing the antiretroviral drug DPV. These reservoir-type rod implants (length 40 mm, cross-sectional diameters 2.5, 3.2, 3.5 or 4.0 mm) comprised a silicone elastomer core containing solid crystalline DPV (loading 10, 20 or 40 % w/w) and an open-ended non-medicated rate-controlling silicone elastomer membrane (thickness 0.5, 0.8 or 1.0 mm). DPV <em>in vitro</em> release rates could be modulated by adjusting the membrane thickness. Continuous <em>in vitro</em> DPV release ∼12 μg/day was demonstrated over 330 days, with sufficient residual drug content (∼87 mg/∼95 %) to extend release for at least 5 years. In particular, the study highlights the challenges in designing subdermal implants providing sufficient DPV release to maintain systemic/vaginal concentrations at protective levels.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126524"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The objective of this study was to develop vitamin E nanobarrier contact lenses that can sustain the delivery of an equivalent amount of cysteamine to the cornea as eight drops per day regimen used in treating cystinosis. Senofilcon A lenses (14.0 mm diameter, −0.50 D power, 8.4 mm base curve) integrated with vitamin E and cysteamine were tested for drug release and fitted to the sink-release model to determine diffusivity and partition coefficient. The pharmacokinetics of cysteamine delivery by contact lenses and by control eye drops was measured in New Zealand white rabbits. Cysteamine delivery was modeled by a mechanistic model using contact lens parameters obtained from the in vitro studies along with known anatomical, physiological and drug specific parameters obtained from literature. The release duration of cysteamine increased from a few minutes in control lenses to about 2 and 6 h, in lenses loaded with 20 and 30 % vitamin E, respectively. In vivo studies showed that the contact lens-based approach can deliver significantly high concentrations compared to eye drops. The total mass of drug delivered by 20 % vitamin E loaded contact lens is more than six times the mass delivered by a single eye drop. The contact lens-based therapy achieves higher delivery than drops in the back of the eye tissues as well. The predictions of the mechanistic mathematical model are in good agreement with in vivo measurements for both eye drops and contact lenses. The contact lens-based delivery of cysteamine is a promising approach for replacing the multiple drop therapy.
{"title":"Cysteamine-eluting contact lenses: integrating in vitro, in vivo, and in silico approaches for ocular drug delivery","authors":"Anuj Chauhan , Sarbani Hazra , Brock Matter , Pankaj Kumar Sharma , Shilpa George , Aishee Dey , Bommanahalli Nagaraju Kumara , Uday B. Kompella","doi":"10.1016/j.ijpharm.2025.126528","DOIUrl":"10.1016/j.ijpharm.2025.126528","url":null,"abstract":"<div><div>The objective of this study was to develop vitamin E nanobarrier contact lenses that can sustain the delivery of an equivalent amount of cysteamine to the cornea as eight drops per day regimen used in treating cystinosis. Senofilcon A lenses (14.0 mm diameter, −0.50 D power, 8.4 mm base curve) integrated with vitamin E and cysteamine were tested for drug release and fitted to the sink-release model to determine diffusivity and partition coefficient. The pharmacokinetics of cysteamine delivery by contact lenses and by control eye drops was measured in New Zealand white rabbits. Cysteamine delivery was modeled by a mechanistic model using contact lens parameters obtained from the in vitro studies along with known anatomical, physiological and drug specific parameters obtained from literature. The release duration of cysteamine increased from a few minutes in control lenses to about 2 and 6 h, in lenses loaded with 20 and 30 % vitamin E, respectively. In vivo studies showed that the contact lens-based approach can deliver significantly high concentrations compared to eye drops. The total mass of drug delivered by 20 % vitamin E loaded contact lens is more than six times the mass delivered by a single eye drop. The contact lens-based therapy achieves higher delivery than drops in the back of the eye tissues as well. The predictions of the mechanistic mathematical model are in good agreement with in vivo measurements for both eye drops and contact lenses. The contact lens-based delivery of cysteamine is a promising approach for replacing the multiple drop therapy.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126528"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10Epub Date: 2026-01-02DOI: 10.1016/j.ijpharm.2026.126554
Ilaria Polidori , Leonie Iris Weber , Stefan Keim , Dennis To , Markus Hartl , Andreas Bernkop-Schnürch
Enzyme-responsive lipid nanoparticles (LNPs) offer a promising strategy for oral nucleic acid delivery to gastrointestinal tumors. We hypothesized that coating LNPs with polyphosphates (PP) would enhance mucus penetration and enable charge conversion upon activation by intestinal alkaline phosphatase (IAP). The presence of the cell-penetrating peptide (CPP) stearyl-D-Arg8 provides enhanced cellular uptake. LNPs were characterized regarding size, polydispersity index, zeta potential, charge conversion and evaluated for pH stability, behaviour in biorelevant fluids, and mucus diffusion. Plasmid DNA encoding for GFP or brain acid soluble protein-1 (BASP1) was encapsulated, and uptake and transfection were studied in intestinal cancer cell lines. Upon incubation with IAP, PP-coated D-Arg8-LNPs released phosphate groups and underwent charge conversion. These particles remained stable across pH 1.5–9.0 and were more resistant to biorelevant fluids, though destabilization occurred with digestive enzymes. Compared to DOTAP- and D-Arg8-LNPs, PP-coated LNPs showed superior mucus diffusion, cellular uptake, and transfection efficiency in hard-to-transfect Caco-2 and SW480 cells. Importantly, BASP1 expression from LNPs effectively suppressed SW480 proliferation. Overall, PP coated LNPs for oral administration can efficiently deliver nucleic acids into intestinal tumor cells, which may be suitable to interfere with the tumorigenic phenotype.
{"title":"Alkaline phosphatase-triggered charge converting lipid nanoparticles: An innovative approach for oral nucleic acid delivery","authors":"Ilaria Polidori , Leonie Iris Weber , Stefan Keim , Dennis To , Markus Hartl , Andreas Bernkop-Schnürch","doi":"10.1016/j.ijpharm.2026.126554","DOIUrl":"10.1016/j.ijpharm.2026.126554","url":null,"abstract":"<div><div>Enzyme-responsive lipid nanoparticles (LNPs) offer a promising strategy for oral nucleic acid delivery to gastrointestinal tumors. We hypothesized that coating LNPs with polyphosphates (PP) would enhance mucus penetration and enable charge conversion upon activation by intestinal alkaline phosphatase (IAP). The presence of the cell-penetrating peptide (CPP) stearyl-D-Arg<sub>8</sub> provides enhanced cellular uptake. LNPs were characterized regarding size, polydispersity index, zeta potential, charge conversion and evaluated for pH stability, behaviour in biorelevant fluids, and mucus diffusion. Plasmid DNA encoding for GFP or brain acid soluble protein-1 (BASP1) was encapsulated, and uptake and transfection were studied in intestinal cancer cell lines. Upon incubation with IAP, PP-coated D-Arg<sub>8</sub>-LNPs released phosphate groups and underwent charge conversion. These particles remained stable across pH 1.5–9.0 and were more resistant to biorelevant fluids, though destabilization occurred with digestive enzymes. Compared to DOTAP- and D-Arg<sub>8</sub>-LNPs, PP-coated LNPs showed superior mucus diffusion, cellular uptake, and transfection efficiency in hard-to-transfect Caco-2 and SW480 cells. Importantly, BASP1 expression from LNPs effectively suppressed SW480 proliferation. Overall, PP coated LNPs for oral administration can efficiently deliver nucleic acids into intestinal tumor cells, which may be suitable to interfere with the tumorigenic phenotype.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126554"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10Epub Date: 2025-12-28DOI: 10.1016/j.ijpharm.2025.126540
Siqi Chen, Yizhen Yan, Jiayi Zou, Xin He, Kexin Li
Multi-modal combination therapy for tumors can overcome the limitations of single-modal therapy and bring new opportunities for high-efficient tumor treatment. Nevertheless, how to ingeniously design functionalized nanocarriers to mediate the synergistict effects among various therapeutic approaches remains a core challenge. In this study, we developed a polydopamine (PDA) coated outside and glucose oxidase (GOx) adsorbed inside copper-doped zeolitic imidazolate framework-8 (CZ8) with metformin hydrochloride (MET) / doxorubicin (DOX) as a multifunctional nano-codelivery system, abbreviated as PMDGCZ8, which could focus more on the synergy and continuity of multiple therapies including photothermal therapy (PTT), chemodynamic therapy (CDT), starving tumor therapy (STT) and chemotherapy (CT). Herein, PMDGCZ8 innovatively combined the gating effect of PDA membrane with the pH sensitivity of CZ8 skeleton to form a dual-responsive bomb that could trigger release on demand and significantly improve the accuracy of tumor localization. Furthermore, we also incorporated the strategies of reshaping the tumor hypoxia and immunosuppressive microenvironment into the synergistic treatment process in order to achieve a comprehensive anti-tumor ecological network. Both in vitro and in vivo experiments suggested that PMDGCZ8 significantly enhanced drug accumulation on tumors, reduced systemic toxicity, activated anti-tumor immune response, further inhibited the recurrence and metastasis, and consequently was expected to become a new type of nano-delivery platform with great development potential.
{"title":"An intelligent responsive ZIF-8 co-delivery nanoplatform with multimodal synergistic technologies for closed-loop therapy of tumors","authors":"Siqi Chen, Yizhen Yan, Jiayi Zou, Xin He, Kexin Li","doi":"10.1016/j.ijpharm.2025.126540","DOIUrl":"10.1016/j.ijpharm.2025.126540","url":null,"abstract":"<div><div>Multi-modal combination therapy for tumors can overcome the limitations of single-modal therapy and bring new opportunities for high-efficient tumor treatment. Nevertheless, how to ingeniously design functionalized nanocarriers to mediate the synergistict effects among various therapeutic approaches remains a core challenge. In this study, we developed a polydopamine (PDA) coated outside and glucose oxidase (GOx) adsorbed inside copper-doped zeolitic imidazolate framework-8 (CZ8) with metformin hydrochloride (MET) / doxorubicin (DOX) as a multifunctional nano-codelivery system, abbreviated as PMDGCZ8, which could focus more on the synergy and continuity of multiple therapies including photothermal therapy (PTT), chemodynamic therapy (CDT), starving tumor therapy (STT) and chemotherapy (CT). Herein, PMDGCZ8 innovatively combined the gating effect of PDA membrane with the pH sensitivity of CZ8 skeleton to form a dual-responsive bomb that could trigger release on demand and significantly improve the accuracy of tumor localization. Furthermore, we also incorporated the strategies of reshaping the tumor hypoxia and immunosuppressive microenvironment into the synergistic treatment process in order to achieve a comprehensive anti-tumor ecological network. Both in vitro and <em>in vivo</em> experiments suggested that PMDGCZ8 significantly enhanced drug accumulation on tumors, reduced systemic toxicity, activated anti-tumor immune response, further inhibited the recurrence and metastasis, and consequently was expected to become a new type of nano-delivery platform with great development potential.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126540"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145862390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Near-infrared (NIR) spectroscopy is a nondestructive analytical technique that is increasingly considered for inclusion in Process Analytical Technology (PAT) frameworks and for 100% inspection, with the potential to raise pharmaceutical product quality. While reflectance-based NIR systems already deliver throughputs suitable for commercial manufacturing, transmission-based NIR systems, although offering superior predictive accuracy for active pharmaceutical ingredient (API) content in tablets, have been throughput-limited. Recently, a newly developed transmission NIR spectrometer has been shown to acquire precise tablet spectra within a few milliseconds. In this study, a spectrometer was integrated into a belt-conveyor transport apparatus to create a high-throughput analytical system for pharmaceutical tablets. A throughput of 186,000 tablets per hour was achieved, demonstrating 100% API content measurement and real-time rejection of out-of-specification tablets.
{"title":"A commercial-scale high-throughput near-infrared transmission spectroscopy system for full inspection of active pharmaceutical ingredient content in all tablets","authors":"Junki Sahara , Katsuhiko Nishiyama , Kazuki Shinoyama , Aya Ikarashi , Takuma Yokoyama , Shinya Matsuda , Kenji Yoshii , Masaya Fujimoto , Yasufumi Yagisawa , Koji Nakayama , Tomoaki Sakamoto","doi":"10.1016/j.ijpharm.2025.126516","DOIUrl":"10.1016/j.ijpharm.2025.126516","url":null,"abstract":"<div><div>Near-infrared (NIR) spectroscopy is a nondestructive analytical technique that is increasingly considered for inclusion in Process Analytical Technology (PAT) frameworks and for 100% inspection, with the potential to raise pharmaceutical product quality. While reflectance-based NIR systems already deliver throughputs suitable for commercial manufacturing, transmission-based NIR systems, although offering superior predictive accuracy for active pharmaceutical ingredient (API) content in tablets, have been throughput-limited. Recently, a newly developed transmission NIR spectrometer has been shown to acquire precise tablet spectra within a few milliseconds. In this study, a spectrometer was integrated into a belt-conveyor transport apparatus to create a high-throughput analytical system for pharmaceutical tablets. A throughput of 186,000 tablets per hour was achieved, demonstrating 100% API content measurement and real-time rejection of out-of-specification tablets.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"690 ","pages":"Article 126516"},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145819254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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